CSIG-02. FOSL1 PROMOTES GLIOMA STEM CELLS TRAITS THROUGH INTERACTING WITH ITS BINDING PROTEIN PHOSPHORYLATED STAT3
نویسندگان
چکیده
Abstract BACKGROUND Glioma stem cells (GSCs) have key roles in tumorigenesis, progression, and resistance to conventional treatments for glioblastoma. We reported that TRPM7 channels, which fused with C-terminal kinase, endow glioma cell-like capacities of self-renewal. Here, we investigated the role downstream target gene FOSL1’s post transcription stemness. METHODS 1) The immunohistochemical staining FOSL1 was performed using rabbit polyclonal anti-FOSL1 antibody tissue arrays from 76 Chinese patients 10 normal individuals. intensity TMA evaluated three different fields (≥100 cells/field). semi-quantitative HSCORE calculated FOSL1. 2) Upon suppression by siRNA FOSL1, GSC markers, CD133 expression flow cytometry PE anti-human antibody, while ALDH1 enzymatic activity assessed an Aldefluor kit, A172 U87MG cell lines patient-derived xenoline PDX-L14 proneural subtype. 3) To assay promoter activity, 5’-flanking region human (1201bp) inserted into firefly luciferase reporter vector pGL3-Basic between MluI BglII sites. For mutant construct, STAT3 binding sites were mutated Q5 site-directed mutagenesis kit. RESULTS Quantification IHC results showed positive nuclear significantly higher GBM (n=13, p=0.0005), grade III (n=12, p=0.0116), II astrocytoma (n=51, p=0.0485) compared brain (n=10). markers positively associated glioma. Phosphorylated directly binds activation levels a effect on transcriptional CONCLUSION Our demonstrated TRPM7-regulated regulated transcription, shed new light TRPM7/FOSL1-directed therapeutics (This study supported NIH NIGMS GM121230)
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ژورنال
عنوان ژورنال: Neuro-oncology
سال: 2022
ISSN: ['1523-5866', '1522-8517']
DOI: https://doi.org/10.1093/neuonc/noac209.151